The Gold Standard in Rapid Screening For Invasive Fungal Infection (IFI)

Fungitell® is the first and the only FDA-cleared and CE marked rapid in vitro diagnostic screening test

for IFI (including Candida, Aspergillus and Pneumocystis) that detects (1g3)-b-D-Glucan in serum.

FUNGITELL® ASSAY

SERUM TEST FOR

(1g3)-b -D-GLUCAN

An FDA-Cleared, 510(k) in vitro diagnostic

Invasive fungal infection: More aggressive medical care, including immunosuppressive therapy and ICU care

has greatly increased the population of patients at risk of invasive fungal infection (IFI). There are an estimated 40-60

thousand invasive fungal infections in the USA annually1. Candidemia represents the 4th leading cause of nosocomial

blood stream infection and the 3rd most common ICU bloodstream infection2.

The low sensitivity and relatively long incubation times of microbial culture, the most widely used diagnostic

technique, has resulted in a need for faster methods with greater sensitivity. With its high sensitivity and rapid

availability of results, the demand for Fungitell® has increased steadily since its clearance by the FDA in 2004.

Early diagnosis and treatment have been shown to have increased survival rates in Candidal Shock3

Delay in Therapy

FUNGITELL® ASSAY THE GOLD STANDARD IN RAPID SCREENING FOR INVASIVE FUNGAL INFECTION

FUNGAL

TRENDS &

STATISTICS

www.fungitell.com1

Administration (Hr): Survival

0-2 ~ 82%

2-6 ~ 65%

6-12 ~ 17%

12-24 ~ 9%

24-72 ~ 8%

Why Test For (1g3)-b-D-Glucan

Most pathogenic fungi* have (1g3)-b-D-Glucan in their

cell walls and minute, but detectable quantities are

released into the circulation during infection. Detection

of elevated levels of (1g3)-b-D-Glucan is an aid to the

presumptive diagnosis of invasive fungal infection (IFI) in

at risk patients.

Multiple studies4,5,6,7,8 have shown glucan to become

elevated well in advance of conventional clinical signs

and symptoms. The early diagnosis of and administration

of therapy for invasive fungal infection is associated

with improved clinical outcome; delayed diagnosis

and therapy is associated with increased mortality9.

Conversely, the elevated morbidity and mortality

associated with invasive fungal infection drives poten-

tially inappropriate systemic antifungal therapy. Research

studies have demonstrated the utility of negative

Fungitell® results to support decisions to withhold or

withdraw antifungals with excellent patient safety.10,11,12

Hence, there is significant utility in the application of

the Fungitell® test in at risk patients.

At Risk Patients

Invasive Fungal Infection is increasing in at risk popula-

tions13 such as:

• Aggressive Care (SICU/MICU/NICU)

• Mechanical Ventilation

• Stem Cell and Organ Transplants

• HIV

• Cancer Treatment

• Diabetes

• Central Venous Catheters

• Hemodialysis

• Gastrointestinal Surgery

• Total Parenteral Nutrition

Opportunities

Fungitell®, an FDA cleared and CE marked diagnostic

test, is used for the detection of (1g3)-b-D-Glucan,

which is frequently associated with the presence of

fungal pathogens. The majority of these are Candida

and Aspergillus species.

There are, potentially, clinical applications that could

benefit from utilizing the (1g3)-b-D-Glucan test where

pneumocystosis is suspected.

The Fungitell® Assay

Features and Benefits

- Provides earlier support for diagnosis of IFI

- Detects glucan from most fungi including

Candida and Aspergillus*

- Rapid results within an hour

- FDA Cleared

- CE Marked

FUNGITELL® ASSAY THE GOLD STANDARD IN RAPID SCREENING FOR INVASIVE FUNGAL INFECTION

www.fungitell.com 2

www.fungitell.com3

Principle of the Fungitell® Reagent

Fungitell® is a (1g3)-b-D-Glucan specific Limulus ame-

bocyte lysate (LAL) reagent containing a chromogenic

peptide substrate. (1g3)-b-D-Glucan in the sample

causes activation of serine proteases. An activated

protease cleaves p-nitroaniline (pNA) from the peptide

substrate and the free pNA is measured at 405 nm.

The test is run in a standard incubating plate reader.

Materials Supplied with the Kit

• 2 vials Fungitell® Reagent

• 2 vials Pyrosol® Reconstitution Buffera

• 2 vials Glucan Standard

• 2 bottles Reagent Grade Water,a 20 mL

• 2 vials Alkaline Pretreatment Solution a

Storage Conditions

Store all reagents at 2-8°C in the dark. Reconstituted

Fungitell® reagent should be stored at 2-8°C and used

within 2 hours. Alternatively, reconstituted Fungitell®

reagent can be frozen at -20°C for 20 days, thawed

once and used.

Materials Required but not Supplied

All materials and glassware must be free of inter-

fering glucan. Dry heat depyrogenation is effective in

eliminating interfering levels of (1g3)-b-D-Glucan

from glass surfaces.

Purchase supplies from a supplier that will certify the

materials free of interfering glucan.

• 96-well microplateb

• Repeating Pipette and tips (250 mL; 1000 mL)b

• Test tubes for sample dilution (13 x 100 mm)b

• Glass pipettes – not plastic

• Parafilm®

• Incubating plate reader capable of reading

at 405 and 490 nm with appropriate kinetic

software for determination of Vmeanb

• Vortex mixer

Order Information

FT001 Fungitell® Kit-110 test wells

The Fungitell® assay is a highly sensitive, micro-

plate-based test that detects (1g3)-b-D-Glucan in

serum. (1g3)-b-D-Glucan is a cell wall constituent of

most medically important fungi including Candida and

Aspergillus.* (1g3)-b-D-Glucan is normally found at

low levels in the blood of healthy humans. In at risk

patients, serum (1g3)-b-D-Glucan values of at least

80 pg/mL, are highly associated with invasive fungal

infection. Conversely, low levels of (1g3)-b-D-Glucan

have a high negative predictive value for invasive

fungal infection.

(1g3)-b-D-Glucan detection is not subject to the

usual interferences. It is not suppressed by anti-fungal

therapy, nor is the test cross-reactive with other

polysaccharides.

Diagnostic Performance

Multiple studies4,5,6,7,8 in diverse patient groups

have shown sensitivities from 70–100% and high

negative predictive values. A variety of studies also

demonstrate diagnostic utility in Pneumocystis jirovecii

pneumonia14,15.

Rapid Results

The Fungitell® assay is performed entirely within a

microplate well without washing steps. The assay

provides results within an hour.

FUNGITELL®

ASSAY

PRODUCT

INFORMATION

www.fungitell.com 4

Antimicrobial Stewardship

Studies have shown that early discontinuation of

empirical therapy in high-risk ICU patients based on

consecutive negative BDG tests may be a reasonable

strategy, with great potential to reduce the overuse of

antifungals13.

Marketplace Longevity

Fungitell® has over a decade of proven clinical use

and has been referenced in over 125 peer-reviewed

clinical papers.

Warnings, Precautions and Limitations

(see instructions for use for details):

i. The tissue locations of fungal infection and en-

capsulation may affect the serum concentration

of (1g3)-b-D-Glucan.

ii. Some individuals have elevated levels of (1g3)-b-

D-Glucan that fall into the indeterminate zone

of 60 – 79 pg/mL. In such cases, additional testing

is recommended.

iii. Test levels were established in adult subjects.

Infant and pediatric normal levels approach those

of adults. Data for neonates, and infants less than

six months, are lacking.

iv. Off-color or turbid samples such as those that are

grossly hemolyzed, lipemic, or contain excessive

bilirubin may cause interference.

v. Samples obtained by heel or finger stick methods

are unacceptable as the alcohol-soaked gauze

used to prepare the site and/or skin surface-pool-

ing of blood may contaminate the specimens.

vi. Surgical gauzes and sponges can leach high levels

of (1g3)-b-D-Glucan and may contribute to a

transient positive result for the Fungitell® assay.

vii. The serum of hemodialysis patients may contain

high levels of (1g3)-b-D-Glucan when certain

cellulose dialysis membranes are used.

viii. In performing the test, great care must be taken

to avoid contamination.

ix. The use of Fungitell® for purposes other than those

described in the Intended Use section of instruc-

tions for use of the product is neither recommend-

ed nor supported by Associates of Cape Cod, Inc.

References:

1. Pfaller, M.A., (2009) Focus on Fungal Infection 19 Proceedings.

2. Reboli, A.C., (2009) Focus on Fungal Infection 19 Proceedings.

3. Kumar, A et al. Poster 2174 ICAAC 2007

4. Odabasi Z., Mattiuzzi G., Estey E., Kantarjian H., Saeki F., Ridge R., Ketchum P., Finkelman M., Rex J. and Ostrosky-Zeichner L. (2004) Beta-D-Glucan as a diagnostic adjunct for invasive fungal infections: Validation, cutoff development, and performance in patients with Acute Myelogenous Leukemia and Myelodysplastic Syndrome. Clinical Infectious Diseases. 39:199-205.

5. Ostrosky-Zeichner L., Alexander B., Kett D., Vazquez J., Pappas P., Saeki F., Ketchum P., Wingard J., Schiff R., Tamura H., Finkelman M., and Rex J. (2005) Multicenter clinical evaluation of the (1g3)-b-D-Glucan assay as as aid to diagnosis of fungal infections in humans. Clin. Inf. Dis. 41: 654-659.

6. Pazos C., Ponton J., and Del Palacio A. (2005) Contribution of (1g3)-b-D-Glucan chromo-genic assay to diagnosis and therapeutic monitoring of invasive aspergillosis in neutropenic adult patients: A comparison with serial screening for circulating galactomannan. J. Clin. Micro. 43(1): 299-305.

7. Pazos, C., Moragues, M-D., Quindos, G., and del Palacio, A. (2006) Diagnostic potential of (1g3)-b-D-Glucan and anti-Candida albicans germ tube antibodies for the diagnosis and therapeutic monitoring of invasive candidiasis in neutropenic adult patients. Re. Iberoam Micol. 23: 209-215.

8. Ellis, M., Ramadi, B., Finkelman, M., Hedstrom, U., Kristenson, J., Ali-Zadeh, H., and Klingspor, L. (2007) Assessment of the clinical utility of serial b-D-Glucan concentrations in patients with persistent neutropenic fever. J. Med. Microbiol. 57: 287-95.

9. Morrell, M., Fraser, V., and Kollef, M. (2005) Delaying the empiric treatment of Candida bloodstream infection until positive culture results are obtained: a potential risk factor for hospital mortality. Antimicrob. Agents. Chemother. 49: 3640-3645.

10. Prattes, J., Hoenigl, M., Rabensteiner, J., Raggam, R.B., Prueller, F., Zollner-Schwetz, I., Valentin, T., Hönigl, K., Fruhwald, S., and Krause, R. , Serum 1,3–beta-D-glucan for the antifungal treatment stratification at the intensive care unit and the influence of surgery, Mycoses Diagnosis, Therapy and Prophylaxis of Fungal Diseases, June 2014

11. Nucci, M., Nouér, S.A., Esteves, P., Guimarães, T., Breda, G., Grassi de Miranda, B., Queiroz-Telles, F., and Colombo, A.L., Discontinuation of empirical antifungal therapy in ICU patients using 1,3-b-D-glucan, Journal of Antimicrobial Chemotherapy Advance Access. published June 10, 2016.

12. Posteraro, B., Tumbarello, M., De Pascale, G., Liberto, E., Vallecoccia, M.S., De Carolis, E., Di Gravio, V., Trecarichi, E.M., Sanguinetti, M. and Antonelli, M., (1,3)-b-D-Glu-can-based antifungal treatment in critically ill adults at high risk of candidaemia: an observational study, Journal of Antimicrobial Chemotherapy Advance Access published April 28, 2016

13. Enoch et al., (2006) JMM 55:809-818.

14. Marty, F. M., Koo, S., Bryar,and J., Baden, L.R. (2007) (1g3)-b-D-Glucan assay positivity in patients with Pneumocystis (carinii) jirovecii pneumonia. Ann. Int. Med. 147: 70-72.

15. Persat F, Ranque S, Derouin F, Michel-Nguyen A, Picot S, Sulahian A (2008) Contribu-tion of the (1g3)-b-D-Glucan Assay for the Diagnosis of Invasive Fungal Infections. J. Clin. Micro. 36: 1009-1013.

a. Products are free of interfering glucans

b. Available from Associates of Cape Cod, Inc.

*Cryptocuccus, Zygomycetes (such as Absidia, Mucor and Rhizopus) and Blastomyces dermatitidis (infective yeast form) are known to have little or no (1g3)-b-D-Glucan and thus, glucan is not detected during infection with these organisms.

www.fungitell.com

Add 100 µL of Fungitell® lysate reagent into Pyroplate wells.

7 Read report data.8 Fungitell® Assay Report Date:

Patient Beta-Glucan Interpretation

I.D.

pg/mL

~ ~ ~ ~ ~ 35

- ~ ~ ~ ~ ~

70 n/a

~ ~ ~ ~ ~ 290

+

9

Reconstitute glucan stockand make standards.

1Prepare alkaline pre-treatment solution.

2

SET-UP

TEST SAMPLES

Incubate and collect kinetic data at 37º C for 40 minutes.

4Reconstitute Fungitell® Reagent.

5

100µL

Pipette 5 µL of sample into Pyroplate wells.

5µL

Add 20 µL of alkaline pretreatment solution into Pyroplate sample wells.

3

20µL

Add 25 µL standards to Pyroplate.

6

25µL

2

Incubate at 37º C for 10 minutes.

5

NOTE: For complete test procedure refer to Fungitell® Instructions For Use (IFU).

FUNGITELL® ASSAY TEST PROCEDURE OUTLINE

SET-UP

TEST SAMPLES

Add 100 µL of Fungitell® lysate reagent into Pyroplate wells.

7 Read report data.8 Fungitell® Assay Report Date:

Patient Beta-Glucan Interpretation

I.D.

pg/mL

~ ~ ~ ~ ~ 35

- ~ ~ ~ ~ ~

70 n/a

~ ~ ~ ~ ~ 290

+

9

Reconstitute glucan stockand make standards.

1Prepare alkaline pre-treatment solution.

2

SET-UP

TEST SAMPLES

Incubate and collect kinetic data at 37º C for 40 minutes.

4Reconstitute Fungitell® Reagent.

5

100µL

Pipette 5 µL of sample into Pyroplate wells.

5µL

Add 20 µL of alkaline pretreatment solution into Pyroplate sample wells.

3

20µL

Add 25 µL standards to Pyroplate.

6

25µL

2

Incubate at 37º C for 10 minutes.

www.fungitell.com 6

About Beacon

The Beacon Diagnostics® Laboratory is a fully CLIA-certified

reference laboratory specializing in (1g3)-b-D-Glucan analysis

services to support the diagnosis of Invasive Fungal Infection

(IFI). Serving clinical and reference laboratories, we offer a

rapid, cost-effective alternative to in-house testing.

The laboratory is a division of Associates of Cape Cod, Inc. The

expert staff at Beacon Diagnostics® Laboratory provides clients

with rapid diagnostic and analytical service, to assist in the

medical evaluation of patients suspected of having invasive

fungal infection. Our laboratory also tests veterinary samples.

We currently hold certifications and licenses in Massachusetts,

California, Florida, Maryland, New York, Pennsylvania and

Rhode Island. An updated list can be found on our website at

www.BeaconDiagnostics.com.

Additional information concerning the applications and latest

findings of (1g3)-b-D-Glucan testing in patients can also be

found on our website.

Hours of Operation

Testing: Mon.-Fri., 8:00 a.m. to 6:00 p.m. EST

Sample Receiving: Mon.-Sat., 8:00 a.m. to 7:00 p.m. EST

CLIA License Number: 22D1021258

Test Information and Sample Requirements

Pricing and Current Procedure Terminology (CPT) Coding

• Call for Pricing

• The Fungitell® assay does not have an assigned CPT code.

Commonly accepted laboratory practice for coding a diag-

nostic test is to seek an existing CPT code that exactly de-

scribes the test; i.e. the organism, methodology, analyte and

sample, as appropriate. If there is no exact match, then a code

is chosen that most closely describes the laboratory procedure

on the basis of methodology. Based on comparison of the

test characteristics to the CPT code description, commonly ac-

cepted coding practice may allow coding for Fungitell® using

87449. The coding preferred by individual payers may vary.

Please check with your payer for specific billing instructions.

Testing and Turn-around Time

Testing is performed Monday through Friday. Typical turnaround

time is about 48 hours from receipt of sample at our facility,

but most results are available the same day they are received.

Specimen Requirements

Each sample sent to Beacon Diagnostics® Laboratory for testing

must be accompanied by a completed Sample Submission Form.

Forms can be obtained by calling (800) 568–0058 or by visiting

our website at www.BeaconDiagnostics.com.

• Please provide at least 0.5 mL of serum separated from the clot

and shipped cold or frozen on ice packs or dry ice. Secure the

vial closure with Parafilm® or tape. Next day shipping is required.

• Serum should be shipped in a sterile, clean, screw-cap plastic

vial (most cryogenic vials certified DNAse and RNAse free are

typically suitable for use). Do not send serum in glass tubes.

Samples not separated from the clot prior to shipment may

incur an additional handling and preparation fee.

• Avoid contact between the serum and potential sources of

(1g3)-b-D-Glucan contamination including cellulosic filters,

gauze, and cotton swabs.

• Hemolyzed, lipemic, and icteric samples are not suitable for

testing.

• Samples must be shipped in accordance with federal shipping

requirements for Clinical Diagnostic Specimens.

• Use Red Top Tubes

• Heel and finger stick samples are inappropriate

• Our laboratory also tests veterinary samples.

Note: To maintain optimal sample temperatures during transit,

especially during the warm summer months, it is advisable to

use insulated shipping containers (e.g. Styrofoam liners) and

extra cold packs or dry ice when shipping samples.

Contact Information

Beacon Diagnostics® Laboratory

124 Bernard E. Saint Jean Dr., E. Falmouth, MA 02536

Technical information and sample submission:

Tel: (800) 568–0058 • Fax: (508) 444–1481

E-mail: info@beacondiagnostics.com

Corporate HeadquartersAssociates of Cape Cod, Inc.124 Bernard E. Saint Jean DriveEast Falmouth, MA 02536-4445 USATel: (888) 395–ACC1(2221) or(508) 540–3444Fax: (508) 540–8680www.acciusa.comCustomer Service:custservice@acciusa.comTechnical Service:techservice@acciusa.comContract Test Service:testservice@acciusa.com

United KingdomAssociates of Cape Cod Int’l., Inc.Deacon Park, Moorgate RoadKnowsley, Liverpool L33 7RXUnited KingdomTel: (44) 151–547–7444Fax: (44) 151–547–7400E-mail: info@acciuk.co.ukwww.acciuk.co.ukCompany Registration Number:BR002906

GermanyAssociates of Cape Cod Europe GmbHOpelstrasse 14D-64546 Mörfelden-WalldorfGermanyTel: (49) 61 05–96 10 0Fax: (49) 61 05–96 10 15E-mail: service@acciusa.dewww.acciusa.de

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